Neoplasms contain increased quantities of O-alkyl lipids. In order to detect surface membrane abnormalities in malignant versus non-malignant tumors, we are measuring the O-alkyl lipid content in these membranes by a procedure which isolates these structures as vesicles from a microsomal preparation. O-alkyl lipids of several tumors have now been quantitated by photo densitometry. We have measured O-alkyl and alk-1-enyl lipids of surface membranes of several metastasizing and non-metastasizing tumors. Work now in progress concerns the measurement of a larger series of metastasizing and non-metastasizing tumors. The mechanism leading to increased O-alkyl lipid synthesis in Erlich ascites tumor cells may involve a decrease in long chain fatty alcohol dehydrogenase activity. Thus, fatty alcohol metabolism may be shunted to O-alkyl lipid synthesis. It is also possible that fatty alcohol synthesis from fatty acids may be increased in neoplasms. We have recently obtained data on alcohol dehydrogenase activity in several solid tumors and compared these results with alcohol dehydrogenase activity in normal tissues. Further work will be necessary before any conclusions can be drawn. We have published evidence to show that the O-alkyl lipid bond is formed by the intermediacy of an endiol of acyl-dihydroxyacetone-phosphate. In the absence of fatty alcohol, this mechanism requires the formation of dihydroxyacetone-phosphate which has exchanged the pro-R hydrogen, and the release of fatty acid which has retained both carboxyl oxygens. We have recently demonstrated the release of dihydroxyacetone-phosphate which has exchanged the pro-R hydrogen and we are currently investigating whether or not the fatty acid which is released contains both carboxyl oxygens.